Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans
Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans
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DOI：
10.1038/ki.2008.701
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发表时间：
2009-04-01
影响因子：
19.6
通讯作者：
Bowden, Donald W.
中科院分区：
文献类型：
--
作者：
Freedman, Barry I.;Hicks, Pamela J.;Bowden, Donald W.
非裔美国人有高发病率的终末期肾病（ESRD）标记为由于高血压。由于最近的研究表明，在这个种族群体中，特发性和HIV相关的局灶节段性肾小球硬化症和非肌肉肌球蛋白重链9（MYH9）基因多态性具有很强的相关性，我们检测了MYH9与各种肾脏疾病的相关性。在175名患有慢性肾小球肾炎相关ESRD的非洲裔美国人，696名患有高血压相关ESRD的非洲裔美国人和948名无肾脏疾病的对照受试者中评估了15个MYH9单核苷酸多态性。在所有871例非糖尿病ESRD患者中，检测到15种多态性中的14种存在显著相关性。仅在高血压相关的ESRD病例中，发现13个MYH9多态性和先前报道的E1单倍型存在显著相关性。因此，在非洲裔美国人中，高血压相关的ESRD与MYH9基因多态性密切相关，这可能解释了高血压肾硬化症患者对血压控制的不良反应。许多被归类为高血压相关ESRD的非洲裔美国人可能患有隐匿性MYH9相关节段性或全球性肾小球硬化症。我们的研究表明，基因-环境和/或基因-基因相互作用可能会引发遗传易感个体的肾脏疾病，因为MYH9风险等位基因纯合子的非裔美国人并不普遍发展为肾脏疾病。
African Americans have high incidence rates of end-stage renal disease (ESRD) labeled as due to hypertension. As recent studies showed strong association with idiopathic and HIV-related focal segmental glomerulosclerosis and non-muscle myosin heavy chain 9 (MYH9) gene polymorphisms in this ethnic group, we tested for MYH9 associations in a variety of kidney diseases. Fifteen MYH9 single-nucleotide polymorphisms were evaluated in 175 African Americans with chronic glomerulonephritis-associated ESRD, 696 African Americans reportedly with hypertension-associated ESRD, and 948 control subjects without kidney disease. Significant associations were detected with 14 of the 15 polymorphisms in all 871 non-diabetic patients with ESRD. In hypertension-associated ESRD cases alone, significant associations were found with 13 MYH9 polymorphisms and the previously reported E1 haplotype. Thus, hypertension-associated ESRD in African Americans is substantially related to MYH9 gene polymorphisms and this may explain the poor response to blood pressure control in those diagnosed with hypertensive nephrosclerosis. It is possible that many African Americans classified as having hypertension-associated ESRD have occult MYH9-associated segmental or global glomerulosclerosis. Our study shows that gene-environment and/or gene-gene interactions may initiate kidney disease in genetically susceptible individuals, because African Americans homozygous for MYH9 risk alleles do not universally develop kidney disease.